title: CXCR5 polymorphisms in non-Hodgkin lymphoma risk and prognosis.
abstract: CXCR5 [chemokine (C-X-C motif) receptor 5; also known as Burkitt lymphoma receptor 1 (BCR1)] is expressed on mature B-cells, subsets of CD4+ and CD8+ T-cells, and skin-derived migratory dendritic cells. Together with its ligand, CXCL13, CXCR5 is involved in guiding B-cells into the B-cell zones of secondary lymphoid organs as well as T-cell migration. This study evaluated the role of common germline genetic variation in CXCR5 in the risk and prognosis of non-Hodgkin lymphoma (NHL) using a clinic-based study of 1,521 controls and 2,694 NHL cases including 710 chronic lymphocytic leukemia/small lymphocytic lymphoma, 586 diffuse large B-cell lymphoma (DLBCL), 588 follicular lymphoma (FL), 137 mantle cell lymphoma (MCL), 230 marginal zone lymphoma (MZL), and 158 peripheral T-cell lymphoma (PTCL). Of the ten CXCR5 tag SNPs in our study, five were associated with risk of NHL, with rs1790192 having the strongest association (OR 1.19, 95% CI 1.08-1.30; p = 0.0003). This SNP was most strongly associated with the risk of FL (OR 1.44, 95 % CI 1.25-1.66; p = 3.1 × 10(-7)), with a lower degree of association with DLBCL (OR 1.16, 95% CI 1.01-1.33; p = 0.04) and PTCL (OR 1.29, 95 % CI 1.02-1.64; p = 0.04) but no association with the risk of MCL or MZL. For FL patients that were observed as initial disease management, the number of minor alleles of rs1790192 was associated with better event-free survival (HR 0.64; 95% CI 0.47-0.87; p = 0.004). These results provide additional evidence for a role of host genetic variation in CXCR5 in lymphomagenesis, particularly for FL.
authors.affiliation: Department of Health Sciences Research, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.
authors.forename: Bridget
authors.initials: B
authors.lastname: Charbonneau
authors.forename: Alice H
authors.initials: AH
authors.lastname: Wang
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.forename: Yan W
authors.initials: YW
authors.lastname: Asmann
authors.forename: Clive S
authors.initials: CS
authors.lastname: Zent
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.forename: George J
authors.initials: GJ
authors.lastname: Weiner
authors.forename: Nazan
authors.initials: N
authors.lastname: Ozsan
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Feldman
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Novak
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
mesh_terms: D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D054380:Receptors, CXCR5 / Q000235:genetics*; D012307:Risk Factors
chemical_list: C095085:CXCR5 protein, human; D054380:Receptors, CXCR5